Abstract
The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, can predict the prognosis of neurodegenerative diseases. However, the significance of NLR for the prognosis of multiple system atrophy (MSA) has not been reported. We aimed to examine the prognostic significance of NLR in MSA. A total of 169 MSA patients and 163 matched healthy controls (HCs) were enrolled. MSA patients were divided into three groups according to the tertiles of their NLR. Kaplan–Meier survival analysis and Cox regression model were used to assessing the effect of NLR on survival. An independent validation cohort of 56 consecutive patients with probable MSA who met the inclusion criteria was included. The NLR was significantly higher in patients with MSA than that in HCs. The survival duration in patients with MSA in group 3 was shorter than that in patients in the other two groups (P = 0.013). In the multivariable Cox regression model, a higher NLR increased the risk of mortality in patients with MSA after adjusting for confounding factors (HR = 1.922, P = 0.035). Additionally, a higher NLR increased the risk of mortality in MSA with predominant cerebellar ataxia (MSA-C) (HR = 2.398, P = 0.033) and in men (HR = 3.483, P = 0.027). The concordance index for the multivariate Cox regression model was more than 0.7 both in the primary cohort and external validation cohort. Patients with MSA had a higher NLR than did HCs. A high NLR increased the risk of mortality with MSA, especially in MSA-C and in men.
Highlights
Multiple system atrophy (MSA) is a severe, progressive neurodegenerative disease that is clinically characterized by varying degrees of parkinsonism, cerebellar ataxia, dysautonomia, and pyramidal features[1]
The pathological hallmark of MSA is abundant argyrophilic filamentous glial cytoplasmic inclusions (GCIs)1. α-Synuclein is the major component of GCIs, and α-synucleinopathy is classified as MSA, Parkinson’s disease (PD), and dementia with Lewy bodies (DLB)[3]
We found that neutrophil-to-lymphocyte ratio (NLR) was not associated with disease progression of MSA (P > 0.05), according to Spearman’s correlation analysis (Supplementary Table 1)
Summary
Multiple system atrophy (MSA) is a severe, progressive neurodegenerative disease that is clinically characterized by varying degrees of parkinsonism, cerebellar ataxia, dysautonomia, and pyramidal features[1]. The pathological features of MSA include widespread neuronal loss in the basal ganglia, cerebellum, pons, inferior olivary nuclei, and spinal cord, accompanied by gliosis[1]. This correlates with the heterogeneity of the clinical presentation of MSA. Α-Synuclein is the major component of GCIs, and α-synucleinopathy is classified as MSA, Parkinson’s disease (PD), and dementia with Lewy bodies (DLB)[3]. Propagation of misfolded α-synuclein from neurons to oligodendroglia and cell-to-cell spreading, oxidative stress, mitochondrial dysfunction, neuroinflammation, and energy failure are potential pathogenic mechanisms[4]
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